• Title/Summary/Keyword: nuclear transplantation

Search Result 104, Processing Time 0.022 seconds

NF-κB and Therapeutic Approach

  • Lee, Chang-Hoon;Kim, Soo-Youl
    • Biomolecules & Therapeutics
    • /
    • v.17 no.3
    • /
    • pp.219-240
    • /
    • 2009
  • Since NF-${\kappa}B$ has been identified as a transcription factor associated with immune cell activation, groups of researchers have dedicated to reveal detailed mechanisms of nuclear factor of ${\kappa}B$ (NF-${\kappa}B$) in inflammatory signaling for decades. The various molecular components of NF-${\kappa}B$ transcription factor pathway have been being evaluated as important therapeutic targets due to their roles in diverse human diseases including inflammation, cystic fibrosis, sepsis, rheumatoid arthritis, cancer, atherosclerosis, ischemic injury, myocardial infarction, osteoporosis, transplantation rejection, and neurodegeneration. With regards to new drugs directly or indirectly modulating the NF-${\kappa}B$ pathway, FDA recently approved a proteasome inhibitor bortezomib for the treatment of multiple myeloma. Many pharmaceutical companies have been trying to develop new drugs to inhibit various kinases in the NF-${\kappa}B$ signaling pathway for many therapeutic applications. However, a gene knock-out study for $IKK{\beta}$ in the NF-${\kappa}B$ pathway has given rise to controversies associated with efficacy as therapeutics. Mice lacking hepatocyte $IKK{\beta}$ accelerated cancer instead of preventing progress of cancer. However, it is clear that pharmacological inhibition of $IKK{\beta}$ appears to be beneficial to reduce HCC. This article will update issues of the NF-${\kappa}B$ pathway and inhibitors regulating this pathway.

Radiological Accident and Acute Radiation Syndrome (방사선 사고와 급성 방사선 증후군)

  • Roh, Hyung-Keun
    • Journal of The Korean Society of Clinical Toxicology
    • /
    • v.9 no.2
    • /
    • pp.39-48
    • /
    • 2011
  • In mass casualty situation due to radiological accidents, it is important to start aggressive management with rapid triage decisions. External contamination needs immediate decontamination and internal contamination should be treated with special expertise and equipment to prevent the rapid uptake of radionuclides by target organs. Acute radiation syndrome shows a sequence of events that varies with the severity of the exposure. More severe exposures generally lead to more rapid onset of symptoms and severe clinical findings. After the massive exposure, various systems of the body reflect their severe damages that can lead to death within hours or up to several months. The disease progression has classically been divided into four stages: prodromal, latent, manifest illness, and recovery or death. Three characteristic clusters of symptoms including the hematopoietic syndrome, the gastrointestinal syndrome and the cerebrovascular syndrome are all associated with the acute radiation syndrome. The standard medical management of the patients with a potentially survivable radiation exposure includes good medical, surgical and supportive measures. Specific treatment with cytokines and bone marrow transplantation should be considered. The management of internal contamination is much the same as the treatment of poisoning. The standard decontamination should be applied to reduce uptake, and the chelating agents can be administered to enhance the clearance of radioisotopes. Radioactive iodine ($^{131}I$) as one of the nuclear fission products can increase the incidence of thyroid cancer in children. Potential benefit of potassium iodide prophylaxis is greater especially in neonates, infants and small children.

  • PDF

Development Ability of Bovine Early Embryo Blastomere In Vitro in Embedding Matrix (체외생산 소 초기배 할구세포의 Embedding Matrix에서의 발생능력)

  • 이홍준;서승운;이상호;송해범
    • Journal of Embryo Transfer
    • /
    • v.10 no.2
    • /
    • pp.171-175
    • /
    • 1995
  • This study was performed to establish the condition and the methods for the techniques of insertion the isolated blastomere cells into cytoplasm, in order to research the develop-mental ability of bovine embryo blastomere cells in vitro produced. After 24h in vitro ovary maturation with the ovaries from a slaughter house, in vitro fertilization was performed to the vital sperms which their mobility were decided by percoll gradient method, with 2~8 cell stage embryos, the blastomeres were isolated in $Ca^2$+. $Mg^2$+-free PBS, and following that embedded into agar and alginate solution, respectively. The rates of in vitro develop-ment are as follows ; in agar embedded 11 among 120(9.2%) 1 /2~1 /3 blastomers cleaved and 6 among 93(6.5%) 1 /4~1 /8 blastomeres cleaved. In sodium alginate-embedded 14 among 84(16.7%) 1 /2~1 /3 blastomeres cleaved and 6 among 85(7.1%) 1 /4~1 /8 blastomeres cleaved. In case of Na-alginate, the rate of the cells were better than those of agar. The results suggest that the techniques for embeeding the isolated blastomeres into gel may help cloning of bovine early embryo without nuclear transplantation.

  • PDF

Polyploidization of Hepatocytes: Insights into the Pathogenesis of Liver Diseases

  • Kim, Ju-Yeon;Choi, Haena;Kim, Hyeon-Ji;Jee, Yelin;Noh, Minsoo;Lee, Mi-Ock
    • Biomolecules & Therapeutics
    • /
    • v.30 no.5
    • /
    • pp.391-398
    • /
    • 2022
  • Polyploidization is a process by which cells are induced to possess more than two sets of chromosomes. Although polyploidization is not frequent in mammals, it is closely associated with development and differentiation of specific tissues and organs. The liver is one of the mammalian organs that displays ploidy dynamics in physiological homeostasis during its development. The ratio of polyploid hepatocytes increases significantly in response to hepatic injury from aging, viral infection, iron overload, surgical resection, or metabolic overload, such as that from non-alcoholic fatty liver diseases (NAFLDs). One of the unique features of NAFLD is the marked heterogeneity of hepatocyte nuclear size, which is strongly associated with an adverse liver-related outcome, such as hepatocellular carcinoma, liver transplantation, and liver-related death. Thus, hepatic polyploidization has been suggested as a potential driver in the progression of NAFLDs that are involved in the control of the multiple pathogenicity of the diseases. However, the importance of polyploidy in diverse pathophysiological contexts remains elusive. Recently, several studies reported successful improvement of symptoms of NAFLDs by reducing pathological polyploidy or by controlling cell cycle progression in animal models, suggesting that better understanding the mechanisms of pathological hepatic polyploidy may provide insights into the treatment of hepatic disorders.

Nanosphere Form of Curcumin Stimulates the Migration of Human Umbilical Cord Blood Derived Mesenchymal Stem Cells

  • Kim, Do-Wan;Kim, Ju Ha;Lee, Sei-Jung
    • Proceedings of the Korean Environmental Sciences Society Conference
    • /
    • 2020.10a
    • /
    • pp.221-221
    • /
    • 2020
  • Curcumin, a hydrophobic polyphenol derived from turmeric, has been used a food additive and as a herbal medicine for the treatment of various diseases. In the present study, we found the functional role of a nanosphere loaded with curcumin (CN) in the promotion of the motility of human umbilical cord blood derived mesenchymal stem cells (hUCB-MSCs) during the wound closure. We found that the efficacy of hUCB-MSCs migration induced by CN was 1000-fold higher than that of curcumin powder. CN significantly increased the motility of hUCB-MSCs by activating c-Src, which is responsible for the phosphorylation of protein kinase C (PKC) and extracellular signal-regulated kinase (ERK). CN induced the expression levels of α-actinin-1, profilin-1 and filamentous-actin, as regulated by the phosphorylation of nuclear factor-kappa B during its promotion of cell migration. In a mouse skin excisional wound model, we found that transplantation of UCB-MSCs pre-treated with CN enhances wound closure, granulation, and re-epithelialization at mouse skin wound sites. These results indicate that CN is a functional agent that promotes the mobilization of UCB-MSCs for cutaneous wound repair.

  • PDF

Reproductive ability of minipigs as surrogates for somatic cell nuclear transfer

  • Joonho Moon;Su-Jin Kim;Jinseok Lee;Hyeyoung Kang;Bumrae Cho;Sung Joo Kim
    • Journal of Animal Science and Technology
    • /
    • v.66 no.1
    • /
    • pp.156-166
    • /
    • 2024
  • Pigs are genetically, anatomically, and physiologically similar to humans. Recently, pigs are in the spotlight as a suitable source animal for xenotransplantation. However, to use pigs as source animals, pigs should be raised in designated pathogen-free facilities. There is abundant data from embryo transfer (ET) experiments using farm pigs as surrogates, but data on ET experiments using minipigs are scarce. Eighty minipigs were used for ET experiments and after transplantation, the implantation and delivery rates were investigated. It was also confirmed whether the pregnancy rate could be increased by changing the condition or surgical method of the surrogate. In the case of minipigs that gave birth, the size of the fetal sac on the 28th day of ET was also measured. The factors that can affect the pregnancy rate such as estrus synchronization program, ovulation status at the time of ET, the number of repeated ET surgeries, and the ET sites, were changed, and the differences on the pregnancy rate were observed. However there were no significant differences in pregnancy rate in minipigs. The diameter of the implanted fetal sac on the 28th day after ET in the minipigs whose delivery was confirmed was calculated to be 4.7 ± 0.5 cm. In conclusion, there were no significant differences in pregnancy rate of minipigs in the comparative experiment on various factors affecting the pregnancy rate. However, additional experiments and analyses are needed due to the large individual differences of the minipigs.

Studies on nuclear transplantation in mouse embryos II. Developmental potential of nuclei from embryos of different developmental stages (생쥐 수정란의 핵이식에 관한 연구 II. 발달단계별 수정란 핵의 이식후 생존성)

  • Park, Choong-saeng;Choe, Sang-yong;Lee, Hyo-jong;Park, Hee-sung
    • Korean Journal of Veterinary Research
    • /
    • v.30 no.4
    • /
    • pp.355-360
    • /
    • 1990
  • Single nuclei from two-, four- and eight-cell mouse embryos were transplanted into enucleated two-cell embryos by micromanipulation and Sendai virus mediated fusion. The developmental potential of these reconstituted embryos in vitro and in vivo was examined. It was found that the single nuclei which were transplanted to enucleated two-cell embryos were not only able to develop to the blastocyst stage in vitro(two-cell nuclei, 76.5%; four-cell nuclei, 68.4%; eight-cell nuclei, 48.3%), but also able to develop to full term in vivo after transfer to recipient mice(two-cell nuclei, 37.1%; four-cell nuclei, 29.6%; eight-cell nuclei, 16.3%). Although the proportion of live young produced after transfer of nucler of nuclear transplant embryos which received eight-cell nuclei was significantly (p<0.05) reduced, it would be suggested that the overall efficiency in producing identical offspring is greater when eight-cell embryos were selected for nuclear donor than two- or four-cell embryos were selected.

  • PDF

Probabilistic Anatomical Labeling of Brain Structures Using Statistical Probabilistic Anatomical Maps (확률 뇌 지도를 이용한 뇌 영역의 위치 정보 추출)

  • Kim, Jin-Su;Lee, Dong-Soo;Lee, Byung-Il;Lee, Jae-Sung;Shin, Hee-Won;Chung, June-Key;Lee, Myung-Chul
    • The Korean Journal of Nuclear Medicine
    • /
    • v.36 no.6
    • /
    • pp.317-324
    • /
    • 2002
  • Purpose: The use of statistical parametric mapping (SPM) program has increased for the analysis of brain PET and SPECT images. Montreal Neurological Institute (MNI) coordinate is used in SPM program as a standard anatomical framework. While the most researchers look up Talairach atlas to report the localization of the activations detected in SPM program, there is significant disparity between MNI templates and Talairach atlas. That disparity between Talairach and MNI coordinates makes the interpretation of SPM result time consuming, subjective and inaccurate. The purpose of this study was to develop a program to provide objective anatomical information of each x-y-z position in ICBM coordinate. Materials and Methods: Program was designed to provide the anatomical information for the given x-y-z position in MNI coordinate based on the Statistical Probabilistic Anatomical Map (SPAM) images of ICBM. When x-y-z position was given to the program, names of the anatomical structures with non-zero probability and the probabilities that the given position belongs to the structures were tabulated. The program was coded using IDL and JAVA language for 4he easy transplantation to any operating system or platform. Utility of this program was shown by comparing the results of this program to those of SPM program. Preliminary validation study was peformed by applying this program to the analysis of PET brain activation study of human memory in which the anatomical information on the activated areas are previously known. Results: Real time retrieval of probabilistic information with 1 mm spatial resolution was archived using the programs. Validation study showed the relevance of this program: probability that the activated area for memory belonged to hippocampal formation was more than 80%. Conclusion: These programs will be useful for the result interpretation of the image analysis peformed on MNI coordinate, as done in SPM program.

Role of NFAT5 in Osteogenic Differentiation of Human Adipose Tissue-Derived Mesenchymal Stem Cells (인체 지방 유래 중간엽 줄기세포의 골분화 조절 기전에서 NFAT5의 역할)

  • Lee, Sun Young;Yang, Ji won;Jung, Jin Sup
    • Journal of Life Science
    • /
    • v.23 no.4
    • /
    • pp.471-478
    • /
    • 2013
  • Human adipose tissue-derived mesenchymal stem cells (hADSCs) have therapeutic potential, including the ability to self-renew and differentiate into multiple lineages. Understanding of molecular mechanisms of stem cell differentiation is important for improving the therapeutic efficacies of stem cell transplantation. In this study, we determined the role of nuclear factor of activated T cells (NFAT5) in the osteogenic differentiation of hADSCs. The down-regulation of NFAT5 expression by the transfection of a specific siRNA significantly inhibited osteogenic differentiation of hADSCs and decreased the activity of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-${\kappa}B$) promoter without affecting their proliferation and adipogenic differentiation. The inhibition of NFAT5 expression inhibited the basal and Tumor Necrosis Factor ${\alpha}$ (TNF-${\alpha}$) induced activation of NF-${\kappa}B$, but it did not affect TNF-${\alpha}$-induced degradation of the $I{\kappa}B$ protein. These findings indicate that NFAT5 plays an important role in the osteogenic differentiation of hADSCs through the modulation of the NF-${\kappa}B$ pathway.

Developing a Gene-trapping Approach for Gene Identification Using Nuclear Transfer in Zebrafish (지브라물고기 복제방법에 의한 유전자 동정 및 유전자트랩법 개발)

  • Lee, K.Y.
    • Journal of Animal Science and Technology
    • /
    • v.46 no.2
    • /
    • pp.155-164
    • /
    • 2004
  • This involves identifying and cloning trapped genes from cultured cells carrying the gene-trap constructs and generating cloned zebrafish using these cells for functional study. Gene-trapping studies in gene-trapped cells were carried out in initial and cloned zebrafish carrying gene-trap events were successfully produced based on the nuclear transplantation technique. Two kind of retroviral gene-trap constructs were adopted. The first one(SA/GFP-TP), constructed in my laboratory, carries a GFP reporter gene containing a splicing acceptor and an internal neo gene. The second one(Neo-TP), obtained from Dr. Hicks (Hicks et al., 1997), contains a promoter-less neo gene located in the LTR sequence of a retroviral vector. The infected cells were subjected to drug selection(neomycin treatment) because the two constructs carry the neomycin resistant gene. All those cells survived the neomycin treatment should carry the proviral insertions. For Neo-TP, Isolated DNA from the neomycin-resistant fibroblast cells infected by Neo-TP, was digested with EcoR1 restriction enzyme and transformed into bacteria after ligation. This procedure led to the isolation of seven clones carrying flanking cellular DNA with a typical retroviral integration signature sequence. These clones contained genomic DNA ranging from 1kb to 7kb and sequences of 300-600 bp were obtained from each of the rescued plasmids. Database searching showed that all of them share high homology to zebrafish sequences. For fish cloning using tagged cells, initially, nucleus donors directly selected from a mixture of cells(Neo-TP cells) were used. A total of 44 embryos(3.7%) out of 1179 transplants were reached blastula stage; 8 of these embryos(0.8%) hatched and 3(0.3%) of them survived to adulthood. One out of three lived cloned zebrafish has an amplified fragment and was labeled with 32P.